The insertion of tendon or ligament into bone (a structure termed the “enthesis”) forms a critical part of a musculoskeletal joint by facilitating safely the transmission of forces between soft tendons/ligaments and hard bones. Undamaged insertions exhibit a transitional region between soft tendon/ligament tissue and stiff bone. Specifically, the insertion transitions from tendon to fibrocartilage to calcified fibrocartilage to bone, thereby representing respective increases in stiffness, gradients in mineral concentration, local changes in cell phenotype, tissue morphology, composition, and mechanical properties thereby preventing abrupt stress concentrations that would potentially cause damage at a non-transitioning soft tissue-hard tissue interface. A notable gradient in tissue composition is the increase in mineral concentration as the tissue transitions from fibrocartilage to bone.
Researchers have suggested that the gradient in insertion stiffness partially depends on local mineral concentration along the insertion length. Upon injury, the insertion's natural features, including the gradient in mineral concentration, are compromised or lost and are not regenerated following natural healing or surgical repair methods. Resulting cost, pain, and physical disability from enthesis injury, coupled with less than satisfactory outcomes from current surgical insertion repair therefore call for an advanced tissue engineering strategy that recapitulates the mechanical and physiological properties of the natural insertion. Current healing and surgical strategies fail to reconstruct the naturally graded structure. Attempts to engineer a mechanically viable insertion require the optimization of mineralization methods capable of stiffening collagen matrices.
Therefore, there is a need for an implantable minerally graded collagen matrix for regeneration along insertions and other tendon/ligament-to-bone interfaces and a method of manipulating the biochemical properties of collagen to regulate mineralization within and on the collagen matrix.